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Volume 14
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Enhanced Expression of Mitochondrial Magmas Protein in Ovarian Carcinomas: Magmas Inhibition Facilitates Antitumour Effects, Signifying a Novel Approach for Ovarian Cancer Treatment

by
Ali Raza
1,2,
Ashfaqul Hoque
3,
Rodney Luwor
1,2,4,†,
Ruth M. Escalona
1,5,6,†,
Jason Kelly
1,
Revati Sharma
1,
Fadi Charchar
2,
Simon Chu
5,6,
Mary K. Short
7,
Paul T. Jubinsky
7,
George Kannourakis
1,2 and
Nuzhat Ahmed
1,2,5,6,8,9,*
1
Fiona Elsey Cancer Research Institute, Ballarat, VIC 3353, Australia
2
Institute of Innovation, Science and Sustainability, Federation University Australia, Health Innovation and Transformation Center, Mount Helen Campus, Ballarat, VIC 3050, Australia
3
St Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, Australia
4
Department of Surgery, Faculty of Medicine, Dentistry and Health Sciences, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia
5
Centre for Endocrinology and Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
6
Department of Molecular & Translational Science, Faculty of Medicine, Nursing and Health Sciences, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia
7
Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, NY 10461, USA
8
Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC 3050, Australia
9
Department of Obstetrics and Gynaecology, Faculty of Medicine, Dentistry and Health Sciences, Royal Women’s Hospital, University of Melbourne, Melbourne, VIC 3050, Australia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2025, 14(9), 655; https://doi.org/10.3390/cells14090655 (registering DOI)
Submission received: 15 March 2025 / Revised: 13 April 2025 / Accepted: 26 April 2025 / Published: 29 April 2025
(This article belongs to the Special Issue Mitochondria and Metabolism in Cancer Stem Cells (CSCs))
Versions Notes

Abstract

Mitochondrial-associated granulocyte macrophage colony-stimulating factor (Magmas) is a unique protein located in the inner membrane of mitochondria, with an active role in scavenging reactive oxygen species (ROS) in cellular systems. Ovarian cancer (OC), one of the deadliest gynaecological cancers, is characterised by genomic instability, affected by ROS production in the tumour microenvironment. This manuscript discusses the role of Magmas and efficacy of its novel small molecule inhibitor BT#9 in OC progression, metastasis, and chemoresistance. Magmas expression levels were significantly elevated in high-grade human OC compared to benign tumours by immunohistochemistry. The inhibition of Magmas by BT#9 enhanced ROS production and reduced mitochondrial membrane permeability, basal respiration, mitochondrial ATP production, and cellular functions, such as the proliferation and migration of OC cell lines in vitro. Oral administration of BT#9 in vivo significantly reduced tumour growth and spread and enhanced the survival of mice without having any effect on the peritoneal organs. These data suggest that Magmas is functionally important for OC growth and spread by affecting ROS levels and that the inhibition of Magmas activity by BT#9 may provide novel clinical benefits for patients with this malignancy.
Keywords: ovarian cancer; Magmas; mitochondria; BT#9; reactive oxygen species; mitochondrial respiration; tumour growth; peritoneal metastasis ovarian cancer; Magmas; mitochondria; BT#9; reactive oxygen species; mitochondrial respiration; tumour growth; peritoneal metastasis

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MDPI and ACS Style

Raza, A.; Hoque, A.; Luwor, R.; Escalona, R.M.; Kelly, J.; Sharma, R.; Charchar, F.; Chu, S.; Short, M.K.; Jubinsky, P.T.; et al. Enhanced Expression of Mitochondrial Magmas Protein in Ovarian Carcinomas: Magmas Inhibition Facilitates Antitumour Effects, Signifying a Novel Approach for Ovarian Cancer Treatment. Cells 2025, 14, 655. https://doi.org/10.3390/cells14090655

AMA Style

Raza A, Hoque A, Luwor R, Escalona RM, Kelly J, Sharma R, Charchar F, Chu S, Short MK, Jubinsky PT, et al. Enhanced Expression of Mitochondrial Magmas Protein in Ovarian Carcinomas: Magmas Inhibition Facilitates Antitumour Effects, Signifying a Novel Approach for Ovarian Cancer Treatment. Cells. 2025; 14(9):655. https://doi.org/10.3390/cells14090655

Chicago/Turabian Style

Raza, Ali, Ashfaqul Hoque, Rodney Luwor, Ruth M. Escalona, Jason Kelly, Revati Sharma, Fadi Charchar, Simon Chu, Mary K. Short, Paul T. Jubinsky, and et al. 2025. "Enhanced Expression of Mitochondrial Magmas Protein in Ovarian Carcinomas: Magmas Inhibition Facilitates Antitumour Effects, Signifying a Novel Approach for Ovarian Cancer Treatment" Cells 14, no. 9: 655. https://doi.org/10.3390/cells14090655

APA Style

Raza, A., Hoque, A., Luwor, R., Escalona, R. M., Kelly, J., Sharma, R., Charchar, F., Chu, S., Short, M. K., Jubinsky, P. T., Kannourakis, G., & Ahmed, N. (2025). Enhanced Expression of Mitochondrial Magmas Protein in Ovarian Carcinomas: Magmas Inhibition Facilitates Antitumour Effects, Signifying a Novel Approach for Ovarian Cancer Treatment. Cells, 14(9), 655. https://doi.org/10.3390/cells14090655

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